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KMID : 0357920100440030272
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Korean Journal of Pathology
2010 Volume.44 No. 3 p.272 ~ p.283
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Gene Expression Profiles of Uterine Normal Myometrium and Leiomyoma and Their Estrogen Responsiveness In Vitro
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Lee Eun-Ju
Prati Bajracharya
Lee Dong-Mok
Cho Kyung-Hyun
Kim Keuk-Jun
Bae Young-Kyung
Kim Mi-Jin
Lee Ki-Ho
Kim Hang-Jin
Song Gun-Ho
Choi In-Ho
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Abstract
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Background: Uterine leiomyomas are common benign smooth muscle tumors among the reproductive aged-women. The research has been aimed to identify the differentially expressed genes between normal myometrium and leiomyoma and to investigate the effects of E2 on their expression.
Methods: Gene microarray analysis was performed to identify the differentially expressed genes between normal myomerium and leiomyoma. The data was confirmed at protein level by tissue microarray.
Results: Gene microarray analysis revealed 792 upregulated genes in leiomyoma. Four genes (tropomyosin 4 [TPM4], collagen, type IV, alpha 2 [COL4α2], insulin-like growth factor binding protein 5 [IGFBP5], tripartite motif-containing 28 [TRIM28]) showed the most dramatic upregulation in all leiomyoma samples. Tissue microarray analyses of 262 sample pairs showed significantly elevated expression of TPM4, IGFBP5, estrogen receptor-α, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4α2 in the forties and fifties age-groups, and TRIM28 in the thirties age-group. PR, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R) and IGFBP5 were induced by E2 in in vitro culture of tissue explants from which cells migrated throughout the plate. Among these, PR, IGF-1, IGFBP5 genes showed higher expression in tissue compared to cells-derived from tissue in leiomyoma and IGF-1R in leiomyoma cell.
Conclusions: This observation implies the importance of the whole tissue context including the cells-derived from tissue in the research for the understanding of molecular mechanism of leiomyoma. Here, we report higher expression of TRIM28 in leiomyoma for the first time and identify E2-responsive genes that may have important roles in leiomyoma development.
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KEYWORD
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Leiomyoma, 17beta-estradiol, Uterus, Oligonucleotide array sequence analysis, Immunohistochemistry
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